title: Shaker-related potassium channels in the central medial nucleus of the thalamus are important molecular targets for arousal suppression by volatile general anesthetics.
abstract: The molecular targets and neural circuits that underlie general anesthesia are not fully elucidated. Here, we directly demonstrate that Kv1-family (Shaker-related) delayed rectifier K(+) channels in the central medial thalamic nucleus (CMT) are important targets for volatile anesthetics. The modulation of Kv1 channels by volatiles is network specific as microinfusion of ShK, a potent inhibitor of Kv1.1, Kv1.3, and Kv1.6 channels, into the CMT awakened sevoflurane-anesthetized rodents. In heterologous expression systems, sevoflurane, isoflurane, and desflurane at subsurgical concentrations potentiated delayed rectifier Kv1 channels at low depolarizing potentials. In mouse thalamic brain slices, sevoflurane inhibited firing frequency and delayed the onset of action potentials in CMT neurons, and ShK-186, a Kv1.3-selective inhibitor, prevented these effects. Our findings demonstrate the exquisite sensitivity of delayed rectifier Kv1 channels to modulation by volatile anesthetics and highlight an arousal suppressing role of Kv1 channels in CMT neurons during the process of anesthesia.
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, Irvine, California 92697-4561, Center for the Neurobiology of Learning and Memory and Department of Anesthesiology and Perioperative Care, University of California, Irvine, Orange, California 92868, and Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California 92697-4025.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Lioudyno
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Birch
authors.forename: Brian S
authors.initials: BS
authors.lastname: Tanaka
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sokolov
authors.forename: Alan L
authors.initials: AL
authors.lastname: Goldin
authors.forename: K George
authors.initials: KG
authors.lastname: Chandy
authors.forename: James E
authors.initials: JE
authors.lastname: Hall
authors.forename: Michael T
authors.initials: MT
authors.lastname: Alkire
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D000077335:Desflurane; D020646:Intralaminar Thalamic Nuclei / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D051637:Shaker Superfamily of Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D055549:Volatile Organic Compounds / Q000494:pharmacology
chemical_list: D018681:Anesthetics, General; D008738:Methyl Ethers; D051637:Shaker Superfamily of Potassium Channels; D055549:Volatile Organic Compounds; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane